Arch Toxicol (2008) 82:893–901 DOI 10.1007/s00204-008-0310-1 123 TOXICOKINETICS AND METABOLISM The inXuence of diet composition on phase I and II biotransformation enzyme induction Jaime L. Rudolf · Kathryn A. Bauerly · Eskouhie Tchaparian · Robert B. Rucker · Alyson E. Mitchell Received: 17 January 2008 / Accepted: 29 April 2008 / Published online: 17 May 2008  Springer-Verlag 2008 Abstract The expression of phase I and II biotransforma- tion enzymes was examined with respect to experimental diet composition and with the addition of the bi-functional inducer Xavone. Enzymatic activity and mRNA levels of cytochrome P450 monooxygenase (CYP) isoforms (CYP1A1, CYP1A2, CYP2B1/2) and glutathione-S-trans- ferase (GST) isoforms (GSTA, GSTM, and GSTP) were used as indices for the changes in expression. An amino acid based (AA) diet and a semi-puriWed egg white (EW) diet were designed to include similar levels of nutrients and were compared to a standard laboratory chow (SC) diet. Rats (Sprague-Dawley) and mice (C57BL/6) were used as animal models. Animals were fed one of the three diets for 7 days prior to incorporation of Xavone (2%, wt/wt). Diets with or without Xavone were next fed for an additional 3 days. Enzymatic activities of the CYPs in mice and GSTs in both mice and rats were determined. In mice, the relative mRNA levels for each of the CYP and GST isoforms were also measured. The increase in phase I and II enzyme expression observed in response to Xavone was most dynamic when the AA-based diet was used (often >20-fold for given isoform enzymatic activities and >200-fold for speciWc mRNAs), followed by the EW diet (10 to 20-fold and 100 to 200-fold, respectively). The SC diet resulted in a higher level of background expression of CYP and GST isoforms and as a consequence the observed fold increases in CYP and GST isoforms (enzymatic and mRNA levels) were substantially less (1 to 10-fold and 1 to 150-fold. respectively), when the SC diet fed group with or without Xavone was compared. Keywords Glutathione S-transferase · GST · Cytochrome P450 monooxygenases · CYP · Diet · Flavone · Flavonoids · Enzyme induction Introduction In nutritional, pharmacological, and toxicological studies, diets are used that range in composition from chemically deWned and semi-puriWed to complex mixtures based on natural products (Ritskes-Hoitinga and Strubbe 2004; National Research Council 1995; Reeves 1993; Bounous et al. 1978). Standard laboratory chow diets are usually cereal-based and usually contain wheat, corn, rice, or soy- bean products, as well as dairy and meat (Ritskes-Hoitinga and Strubbe 2004). These diets are prepared from a wide array of ingredients that are based upon commodity avail- ability and therefore can range in phytochemicals and bio- active xenobiotic content. Subtle diVerences in components will always exist between batches of commercially avail- able chow diets. There are many factors to consider when selecting an appropriate diet (e.g. purity, reproducibility and the ability to meet given requirements) nonetheless; selection is often made based on price or familiarity rather J. L. Rudolf · A. E. Mitchell (&) Department of Food Science and Technology, University of California, Cruess Hall, One Shields Avenue, UC Davis, Davis, CA 95616, USA e-mail: aemitchell@ucdavis.edu K. A. Bauerly · R. B. Rucker Department of Nutrition, University of California, 3135 Meyer Hall, One Shields Avenue, UC Davis, Davis, CA 95616, USA E. Tchaparian Amgen, Inc, 1120 Veterans Blvd, South San Francisco, CA 94080, USA